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Current Role of Adjuvant Therapy for Colon Cancer

Panelists: Johanna C. Bendell,MD, Sarah Cannon Research Institute; Dirk Arnold, MD, PhD, KTB Klinik fur Tumorbiologie GmbH & Co. KG ; Heinz-Josef Lenz, MD, FACP, USC Center for Molecular Pathway and Drug Discovery; Zev A. Wainberg, MD, UCLA Medical Center
Published: Wednesday, Nov 21, 2018



Transcript: 

Johanna C. Bendell, MD:
Thank you for joining us for this OncLive Peer Exchange®. We continue to refine the way we treat patients with advanced colorectal cancers in both the perioperative and the metastatic setting. This OncLive® discussion, “Optimal Treatment for Advanced Colon and Rectal Cancers,” will feature a panel of experts who will join me to discuss the latest in clinical research, including abstracts from the ESMO [European Society for Medical Oncology] 2018 Annual Meeting. We’ll talk about how the newest data pertains to your patient and how to use it in everyday practice.

I am Dr. Johanna Bendell, chief development officer and director of the Drug Development Unit at the Sara Cannon Research Institute in Nashville, Tennessee. Joining me for this panel discussion are:

Dr. Dirk Arnold, professor of medicine, medical director at Hubertus Tumor Center, Hamburg, Germany.

Dr. Heinz-Josef Lenz, a professor of medicine, J. Terrance Lanni chair in gastrointestinal cancer research, and co-director of the USC Center for Molecular Pathway and Drug Discovery in Los Angeles, California.

And Dr. Zev Wainberg, associate professor of medicine and co-director of the UCLA GI Oncology Program of UCLA Medical Center in Santa Monica, California.

Thank you for joining us, let’s begin. So, let’s start talking a bit about locally advanced colon and rectal cancers. You know now we have some new data, and it’s changing practices for patients with adjuvant treatment in colon cancer. So, it’s great to discuss how we now approach adjuvant therapy for patients with colon cancer. Zev, do you want to tell us a little bit about your general approach?

Zev A. Wainberg, MD: Great. So, I think that we’ve known that in colorectal cancer, the majority of patients are going to present with stage II, stage III cancers—the ones who are not metastatic and adjuvant therapy is part of the standard of care. It’s been clear for many years that certainly patients with stage III colon cancers are receiving, by and large, 5-FU–based [fluorouracil] and oxaliplatin-based chemotherapy. The questions that have emerged most recently is, since there’s clearly no role for adding to 5-FU and oxaliplatin-based therapies, the most recent questions have centered on: How can we minimize the extent of the treatment that these patients should receive to limit toxicity and in particular, peripheral neuropathy? And that’s been one major area of focus that we’ll be talking about. Also, are there certain subsets within stage II and stage III [disease] that deserve special attention, with respect to the extent and the duration of what they receive adjuvantly?

Johanna C. Bendell, MD: Very good. And we have Heinz Lenz here, “molecular marker king.” So, if you have a patient that comes to you with earlier stage disease then I think our early-stage answer is going to differ from our later-stage answer.

Heinz-Josef Lenz, MD, FACP: Yes.

Johanna C. Bendell, MD: What are the necessary molecular tests that we’d get for the patient? And what are ones that would be scientifically interesting?
Heinz-Josef Lenz, MD, FACP: I think over the last decade there have been many attempts to better characterize the patients in stage II and stage III disease to decide should we give, or can we spare chemotherapy? But we have been coming out pretty empty-handed, because I think it’s a very complex situation. We are not even able to add target agents to it. So, it’s a completely different scenario in resected disease.

Now, we have heard about Oncotype [Oncotype DX]. It tends to do gene expression analysis and signatures to potentially predict tumor recurrence. I think one of the limitations is, it is changing the recurrent score but it’s not related to the efficacy of adjuvant treatment or the benefit of adjuvant treatment, and that has been the limitation—in the introduction and the take-up of this particular test, and I don’t use it.

So, I think it goes back to what other technologies we have. In addition to recurrent scores, it’s, should we do DNA mutation analysis? Should we do microsatellite instability [MSI]? And I think one of the, maybe, biggest steps forward is probably the MSI testing? The now randomized phase III clinical trials utilize the testing for randomization of patients to active FOLFOX [folinic acid/fluorouracil/oxaliplatin], plus/minus an immune checkpoint inhibitor. And I think that needs to be tested, for a lot of different reasons. Not only for the use in clinical trials, but also for genetic predisposition. It opens up a lot of opportunities. Because it is the only marker which goes along with an indication of treatment in metastatic disease, independent of the primary tumor origin.

There has been a lot of data coming out about if [the] KRAS mutation or BRAF mutation is associated with tumor recurrence, and the data are mixed and basically not consistent. But we know when BRAF [mutations] recur, then the prognosis kicks in. So, it maybe sometimes makes sense to check BRAF-mutantions because if they recur, the clock starts very quickly, and then treatment options for this patient population—which we all know change, and we will talk a little bit later about it—may be very important to know at this time and not starting testing at this time. So, I always do an NGS [next-generation sequencing] panel now for stage II and III disease, just to know that when the tumor recurs, I am ready to go and have potentially new treatments options, which maybe not becoming apparent at that time.


Transcript Edited for Clarity

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Transcript: 

Johanna C. Bendell, MD:
Thank you for joining us for this OncLive Peer Exchange®. We continue to refine the way we treat patients with advanced colorectal cancers in both the perioperative and the metastatic setting. This OncLive® discussion, “Optimal Treatment for Advanced Colon and Rectal Cancers,” will feature a panel of experts who will join me to discuss the latest in clinical research, including abstracts from the ESMO [European Society for Medical Oncology] 2018 Annual Meeting. We’ll talk about how the newest data pertains to your patient and how to use it in everyday practice.

I am Dr. Johanna Bendell, chief development officer and director of the Drug Development Unit at the Sara Cannon Research Institute in Nashville, Tennessee. Joining me for this panel discussion are:

Dr. Dirk Arnold, professor of medicine, medical director at Hubertus Tumor Center, Hamburg, Germany.

Dr. Heinz-Josef Lenz, a professor of medicine, J. Terrance Lanni chair in gastrointestinal cancer research, and co-director of the USC Center for Molecular Pathway and Drug Discovery in Los Angeles, California.

And Dr. Zev Wainberg, associate professor of medicine and co-director of the UCLA GI Oncology Program of UCLA Medical Center in Santa Monica, California.

Thank you for joining us, let’s begin. So, let’s start talking a bit about locally advanced colon and rectal cancers. You know now we have some new data, and it’s changing practices for patients with adjuvant treatment in colon cancer. So, it’s great to discuss how we now approach adjuvant therapy for patients with colon cancer. Zev, do you want to tell us a little bit about your general approach?

Zev A. Wainberg, MD: Great. So, I think that we’ve known that in colorectal cancer, the majority of patients are going to present with stage II, stage III cancers—the ones who are not metastatic and adjuvant therapy is part of the standard of care. It’s been clear for many years that certainly patients with stage III colon cancers are receiving, by and large, 5-FU–based [fluorouracil] and oxaliplatin-based chemotherapy. The questions that have emerged most recently is, since there’s clearly no role for adding to 5-FU and oxaliplatin-based therapies, the most recent questions have centered on: How can we minimize the extent of the treatment that these patients should receive to limit toxicity and in particular, peripheral neuropathy? And that’s been one major area of focus that we’ll be talking about. Also, are there certain subsets within stage II and stage III [disease] that deserve special attention, with respect to the extent and the duration of what they receive adjuvantly?

Johanna C. Bendell, MD: Very good. And we have Heinz Lenz here, “molecular marker king.” So, if you have a patient that comes to you with earlier stage disease then I think our early-stage answer is going to differ from our later-stage answer.

Heinz-Josef Lenz, MD, FACP: Yes.

Johanna C. Bendell, MD: What are the necessary molecular tests that we’d get for the patient? And what are ones that would be scientifically interesting?
Heinz-Josef Lenz, MD, FACP: I think over the last decade there have been many attempts to better characterize the patients in stage II and stage III disease to decide should we give, or can we spare chemotherapy? But we have been coming out pretty empty-handed, because I think it’s a very complex situation. We are not even able to add target agents to it. So, it’s a completely different scenario in resected disease.

Now, we have heard about Oncotype [Oncotype DX]. It tends to do gene expression analysis and signatures to potentially predict tumor recurrence. I think one of the limitations is, it is changing the recurrent score but it’s not related to the efficacy of adjuvant treatment or the benefit of adjuvant treatment, and that has been the limitation—in the introduction and the take-up of this particular test, and I don’t use it.

So, I think it goes back to what other technologies we have. In addition to recurrent scores, it’s, should we do DNA mutation analysis? Should we do microsatellite instability [MSI]? And I think one of the, maybe, biggest steps forward is probably the MSI testing? The now randomized phase III clinical trials utilize the testing for randomization of patients to active FOLFOX [folinic acid/fluorouracil/oxaliplatin], plus/minus an immune checkpoint inhibitor. And I think that needs to be tested, for a lot of different reasons. Not only for the use in clinical trials, but also for genetic predisposition. It opens up a lot of opportunities. Because it is the only marker which goes along with an indication of treatment in metastatic disease, independent of the primary tumor origin.

There has been a lot of data coming out about if [the] KRAS mutation or BRAF mutation is associated with tumor recurrence, and the data are mixed and basically not consistent. But we know when BRAF [mutations] recur, then the prognosis kicks in. So, it maybe sometimes makes sense to check BRAF-mutantions because if they recur, the clock starts very quickly, and then treatment options for this patient population—which we all know change, and we will talk a little bit later about it—may be very important to know at this time and not starting testing at this time. So, I always do an NGS [next-generation sequencing] panel now for stage II and III disease, just to know that when the tumor recurs, I am ready to go and have potentially new treatments options, which maybe not becoming apparent at that time.


Transcript Edited for Clarity
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